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- Title
c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.
- Authors
Yohei Ozawa; Yasuhiro Nakamura; Fumiyoshi Fujishima; Saulo JA Felizola; Kenichiro Takeda; Hiroshi Okamoto; Ken Ito; Hirotaka Ishida; Takuro Konno; Takashi Kamei; Go Miyata; Noriaki Ohuchi; Hironobu Sasano
- Abstract
Background: c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. Methods: The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Results: Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. Conclusions: The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.
- Subjects
SQUAMOUS cell carcinoma; ESOPHAGEAL cancer; HEPATOCYTE growth factor; LIGANDS (Biochemistry); GENE expression; IMMUNOHISTOCHEMISTRY; PROGNOSIS
- Publication
BMC Cancer, 2015, Vol 15, Issue 1, p1
- ISSN
1471-2407
- Publication type
Article
- DOI
10.1186/s12885-015-1450-3